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Background: A new manometric classification of esophageal achalasia has recently been proposed that also suggests a correlation with the final outcome of treatment. The aim of this study was to investigate this hypothesis in a large group of achalasia patients undergoing laparoscopic Heller-Dor myotomy., Methods: We evaluated 246 consecutive achalasia patients who underwent surgery as their first treatment from 2001 to 2009. Patients with sigmoid-shaped esophagus were excluded. Symptoms were scored and barium swallow X-ray, endoscopy, and esophageal manometry were performed before and again at 6 months after surgery. Patients were divided into three groups: (I) no distal esophageal pressurization (contraction wave amplitude <30 mmHg); (II) rapidly propagating compartmentalized pressurization (panesophageal pressurization >30 mmHg); and (III) rapidly propagating pressurization attributable to spastic contractions. Treatment failure was defined as a postoperative symptom score greater than the 10th percentile of the preoperative score (i.e., >7)., Results: Type III achalasia coincided with a longer overall lower esophageal sphincter (LES) length, a lower symptom score, and a smaller esophageal diameter. Treatment failure rates differed significantly in the three groups: I = 14.6% (14/96), II = 4.7% (6/127), and III = 30.4% (7/23; p = 0.0007). At univariate analysis, the manometric pattern, a low LES resting pressure, and a high chest pain score were the only factors predicting treatment failure. At multivariate analysis, the manometric pattern and a LES resting pressure <30 mmHg predicted a negative outcome., Conclusion: This is the first study by a surgical group to assess the outcome of surgery in 3 manometric achalasia subtypes: patients with panesophageal pressurization have the best outcome after laparoscopic Heller-Dor myotomy.

Background: Few studies have reported very long-term results after surgery for oesophageal achalasia. The aim of the present study was to assess long-term subjective outcomes after cardiomyotomy and partial fundoplication, focusing specifically on the risk of oesophageal cancer., Methods: Clinical and demographic information from 228 consecutive patients who had surgery between 1980 and 1992 was extracted from hospital files. Survival status and dates of death were obtained from census offices. Causes of death were obtained from public registries and compared with those of the general population. Symptoms were assessed by means of a questionnaire and endoscopy results were scrutinized., Results: Among 226 patients who could be traced, 182 of 184 survivors were contacted and the cause of death established for 41 of 42 patients. At a median follow-up of 18.3 years, almost 90 per cent of patients were satisfied with the treatment. Four had developed squamous cell oesophageal carcinoma 2, 8, 13 and 18 years after surgery, one of whom was still alive. The standardized mortality ratio for oesophageal carcinoma was significantly higher than expected in men., Conclusion: Cardiomyotomy and partial fundoplication is an excellent long-term treatment for achalasia. Men with achalasia have an increased risk of developing oesophageal cancer.

Objective: Laparoscopic myotomy is the currently preferred treatment for achalasia. Our objectives were to assess the long-term outcome of this operation and preoperative factors influencing said outcome., Methods: Demographic and clinical characteristics and data on long-term outcome were prospectively collected on patients undergoing laparoscopic myotomy for achalasia at our institution from 1992 to 2007. Treatment failure was defined as a postoperative symptom score higher than the 10th percentile of the preoperative score (>9). Logistic regression analysis was used to identify independent preoperative factors associated with successful myotomy., Results: Four hundred seven consecutive patients (220 men, 187 women) underwent the laparoscopic Heller-Dor procedure during the study period; 89 (22%) of them had previously had endoscopic treatment(s). The mortality rate was 0; the conversion and morbidity rates were 1.5% and 1.9%, respectively. The operation failed in 10% of patients (39/407) and the 5-year actuarial probability of being asymptomatic was 87%. Most failures (25/39, 64%) occurred within 12 months of the operation and can be considered as technical failures (incomplete myotomy). Pneumatic dilation overcome the dysphagia in 75% of patients whose surgery was unsuccessful. Considering both the primary surgery and this ancillary treatment, the operation was effective in 97% of achalasia patients. The frequency of sigmoid esophagus, lower esophageal sphincter (LES) resting pressures, and chest pain scores differed statistically between patients with and without recurrences. At multivariate analysis, high preoperative LES pressures (>30 mm Hg) was an independent predictor of a good response. The presence of chest pain and of sigmoid esophagus independently predicted the failure of the procedure., Conclusion: Laparoscopic myotomy can durably relieve dysphagia symptoms. High preoperative LES pressures represent the strongest predictor of a positive outcome, probably reflecting a less severely damaged esophageal muscle.

Objective: The loss of myenteric neurons in the lower esophageal sphincter (LES) characterizes achalasia, an esophageal motor disorder. Because the presence of lymphocytic infiltrates suggests an immuno-mediated mechanism ongoing at the sites of disease, we investigated the T-cell receptor (TCR) repertoire and the ability to recognize human herpes virus type 1 (HSV-1) antigens of LES-infiltrating T lymphocytes in achalasia patients., Methods: Fifty-nine patients with idiopathic achalasia and 38 heart-beating cadaveric multiorgan donors (controls) were studied. By flow cytometry evaluation and CDR3 length spectratyping analysis, the lymphocytes of 18 patients and 15 controls were analyzed, whereas 41 patients and 23 controls were employed for functional assays., Results: Achalasia patients were characterized by a significantly higher esophagus lymphocytic infiltrate than controls (24.71%+/- 3.11 and 9.54%+/- 1.34, respectively; P < 0.05), mainly represented by CD3+CD8+ T cells. The characterization of TCR beta chain repertoire of CD3+ cells showed the expression of a limited number of TCR beta variable (BV) gene families (from two to five out of 26), with highly restricted spectratypes, suggesting a disease-associated oligoclonal selection of T cells. Furthermore, lymphocytes from achalasia LES specifically responded to exposure to HSV-1 antigens in vitro as showed by increased proliferation and Th-1 type cytokines release., Conclusions: These data suggest that the oligoclonal lymphocytic infiltrate within the LES of achalasia patients may represent the trace of an immune-inflammatory reaction triggered by HSV-1 antigens and that the Th1-type cytokines released by the activated lymphocytes may contribute to establish the neuronal damage accounting for the clinical features of idiopathic achalasia.

Laparoscopic Heller myotomy has recently emerged as the treatment of choice for esophageal achalasia. Previous unsuccessful treatments (pneumatic dilations or botulinum toxin [BT] injections) can make surgery more difficult, causing a higher risk of mucosal perforation and jeopardizing the outcome. The study goal was to evaluate the effects of prior endoscopic treatments on laparoscopic Heller myotomy. Between January 1992 and February 2005, 248 patients (130 males and 118 females; median age, 43 years) underwent a laparoscopic Heller-Dor operation for achalasia: 203 underwent primary surgery (group A), 19 had been previously treated with pneumatic dilations (group B), and 26 had BT injections (alone [22] or with dilations [4] (group C)). Median duration of the operation and rate of intraoperative mucosal lesions were not different in the three groups. Median follow-up was 41 months. The 5-year actuarial of control of dysphagia was similar in groups A (86%) and B (94%), whereas only 75% of group C patients were symptom free at 5 years (P = 0.02). On logistic regression analysis, prior treatment with two BT injections or BT combined with dilation was associated with poor outcome of surgery. Further, dilations for surgical failure patients were effective in 80% of group A but in only 33% of group B or C patients. Heller-Dor surgery is safe and effective as a primary or a second-line treatment (after pneumatic dilations or BT injections) for achalasia. However, long-term results seem less satisfactory in patients previously treated with BT.

Background: The aim of this study was to investigate the long-term clinical outcome of the laparoscopic Heller Dor procedure for esophageal achalasia., Methods: A total of 71 consecutive patients with a minimum 6 year follow-up were evaluated. These patients were seen at 1 and 6 months after the operation (at which time barium swallow, endoscopy, manometry, and pH monitoring were performed), and annually thereafter. A dedicated symptom score, that combined severity and frequency of symptoms was used., Results: The median symptom score decreased from 22 (range, 9-29) preoperatively to 4 (range, 0-16) at last follow-up, (p < 0.01). During the follow-up period, 13 patients suffered symptom recurrence; seven of them (54%) had already been diagnosed at the 1-year follow-up. All of these patients were treated with complementary pneumatic dilations. Overall, at a minimum of 6- years after the operation, 81.7% of the patients were satisfied with the treatment and were able to eat normally., Conclusions: The long-term outcome of laparoscopic surgical treatment of esophageal achalasia is only slightly affected by the length of the follow-up and most of the symptomatic failures occur in the early period after the operation.

Background: The treatment of esophageal achalasia is still controversial: current therapies are palliative and aim to relieve dysphagia by disrupting or relaxing the lower esophageal sphincter muscle fibers with botulinum toxin. The aim of this study was to compare the clinical and economic results of two such treatments: laparoscopic myotomy and botulinum toxin injection., Methods: A total of 37 patients with esophageal achalasia were randomly assigned to receive laparoscopic myotomy (20) or two Botox injections 1 month apart (17). All patients were treated at the same hospital and were part of a larger multicenter study. Symptom score, lower esophageal sphincter pressure, and esophageal diameter at barium swallow were compared. The economic analysis was performed considering only the direct costs (cost per treatment and cost effectiveness, i.e., cost per patient healed)., Results: Mortality and morbidity were nil in both groups. The actuarial probability of being asymptomatic at 2 years was 90% for surgery and 34% for Botox (p < 0.05). The initial cost was lower for Botox (1,245 Euros) than for surgery (3,555 Euros), but when cost effectiveness at 2 years was considered, this difference nearly disappeared: Botox 3,364 Euros, surgery 3,950 Euros., Conclusion: Botox is still the least costly treatment, but the minimal difference in the longer term does not justify its use, given that surgery is a risk-free, definitive treatment.

This study was designed to test the hypothesis that mononuclear cells in the myenteric plexus of patients with achalasia may be activated by herpes simplex virus type 1 (HSV-1). Strips of esophageal muscle were obtained from patients with achalasia and multiorgan transplant donors who served as control subjects. After muscle digestion, mononuclear cells were purified through a Percoll gradient and cultured in medium, either alone or containing ultraviolet-inactivated HSV-1 or poliovirus (multiplicity of infection 1:1.5). As an indicator of HSV-1-induced lymphocyte activation, we determined T-cell proliferation by means of 3H-thymidine incorporation and interferon gamma release. DNA was extracted from esophageal muscle of achalasia patients and control subjects, and used as a template for PCR analysis using primer pairs specific for HSV-1. Circulating anti-HSV-1 and HSV-2 antibodies were detected by enzyme-linked immunosorbent assay on serum samples. Fifteen patients with naive achalasia and eight control subjects were studied. The prevalence of circulating anti-HSV-1 and HSV-2 antibodies proved similar in the two groups, and no HSV-1 DNA was detected by polyermase chain reaction in the esophageal muscle samples. The proliferative index in mononuclear cells from achalasia patients stimulated with HSV-1 showed a 3.4-fold increase in comparison with control subjects (P<0.01). In addition, a 1.4-fold increase in interferon gamma release after incubation with HSV-1 was observed in cells from achalasia patients but not control subjects. The results of this study indicate that HSV-1-reactive immune cells are present in lower esophageal sphincter muscles of patients with achalasia. We hypothesize that the HSV-1-reactive lymphocytes in lower esophageal sphincter muscles of achalasia patients may contribute to damage of the neurons in the myenteric plexus and lead to the motor dysfunction.